Electrophysiological and Pharmacological Study on Innervation of the Aganglionic Colon in Hirschsprung's Disease of Human and Murine Model

Abstract

A true role of extrinsic nerve fibres proliferating abundantly in the aganglionic colon of Hirschsprung's disease has not yet been established. Electrophysiological and pharmacological studies were carried out on rectal muscle strips of piebald lethal mice and their siblings. Muscle strips of both aganglionic and normal colon obtained from fifteen patients with Hirschsprung's disease were also investigated for the purpose of determining whether these extrinsic nerve fibres innervate the smooth muscle cells in the aganglionic colon or not. Junction potentials and contractile tensions evoked by electric stimulations were recorded employing the double-sucrose gap method, and examined the effects of nerve blocking agents on junction potentials. In the normal colon, excitatory junction potentials and inhibitory junction potentials were recorded following stimulation in both man and mouse. Excitatory junction potentials were accompanied by muscle contraction and abolished by atropine or tetrodotoxin. Inhibitory junction potentials were resistant to phentolamine and propranolol, and abolished by tetrodotoxin. It was concluded that the normal colon of both mouse and man is innervated by cholinergic excitatory and non-adrenergic inhibitory nerves. In the aganglionic colon, on the other hand, neither junction potentials nor contractions were evoked by stimulations in both mouse and man. These evidences led to the conclusion that in the aganglionic colon in Hirschsprung's disease of man and murine model, there may be a deficiency in neuronal regulation.